|
|
||||||||

* Instituto de Bioquímica (Centro Mixto CSIC-UCM) and
Centro de Citometría de Flujo y Microscopía Confocal, Facultad de Farmacia. Universidad Complutense, 28040 Madrid, Spain
1Correspondence: Instituto de Bioquímica, Facultad de Farmacia, 28040 Madrid. Spain. E-mail: boscal{at}eucmax.sim.ucm.es
Treatment of elicited peritoneal macrophages or the macrophage cell line
RAW 264.7 with high concentrations of nitric oxide donors is followed
by apoptotic cell death. Analysis of the changes in the mitochondrial
transmembrane potential (
m) with specific fluorescent
probes showed a rapid and persistent increase of 
m, a
potential that usually decreases in cells undergoing apoptosis through
mitochondrial-dependent mechanisms. Using confocal microscopy, the
release of cytochrome c from the mitochondria to the
cytosol was characterized as an early event preceding the rise of

m. The cytochrome c from cells treated
with nitric oxide donors was modified chemically, probably through the
formation of nitrotyrosine residues, suggesting the synthesis of
peroxynitrite in the mitochondria. These results indicate that nitric
oxide-dependent apoptosis in macrophages occurs in the presence of a
sustained increase of 
m, and that the chemical
modification and release of cytochrome c from the
mitochondria precede the changes of 
m.Hortelano,
S., Alvarez, A. M., Boscá, L. Nitric oxide induces tyrosine
nitration and release of cytochrome c preceding an
increase of mitochondrial transmembrane potential in macrophages.
Key Words: apoptosis NO nitric oxide synthase mitochondria
This article has been cited by other articles:
![]() |
S.-T. Lee, T.-T. Wu, P.-Y. Yu, and R.-M. Chen Apoptotic insults to human HepG2 cells induced by S-(+)-ketamine occurs through activation of a Bax-mitochondria-caspase protease pathway Br. J. Anaesth., January 1, 2009; 102(1): 80 - 89. [Abstract] [Full Text] [PDF] |
||||
![]() |
M. C. Carreras and J. J. Poderoso Mitochondrial nitric oxide in the signaling of cell integrated responses Am J Physiol Cell Physiol, May 1, 2007; 292(5): C1569 - C1580. [Abstract] [Full Text] [PDF] |
||||
![]() |
H.-J. An, O. Maeng, K.-H. Kang, J.-O. Lee, Y.-S. Kim, S.-G. Paik, and H. Lee Activation of Ras Up-regulates Pro-apoptotic BNIP3 in Nitric Oxide-induced Cell Death J. Biol. Chem., November 10, 2006; 281(45): 33939 - 33948. [Abstract] [Full Text] [PDF] |
||||
![]() |
M. Zeini, P. G. Traves, R. Lopez-Fontal, C. Pantoja, A. Matheu, M. Serrano, L. Bosca, and S. Hortelano Specific Contribution of p19ARF to Nitric Oxide-Dependent Apoptosis. J. Immunol., September 1, 2006; 177(5): 3327 - 3336. [Abstract] [Full Text] [PDF] |
||||
![]() |
M. J. Oursler, E. W. Bradley, S. L. Elfering, and C. Giulivi Native, not nitrated, cytochrome c and mitochondria-derived hydrogen peroxide drive osteoclast apoptosis Am J Physiol Cell Physiol, January 1, 2005; 288(1): C156 - C168. [Abstract] [Full Text] [PDF] |
||||
![]() |
P. Ranjan, P. Shrivastava, S. M. Singh, A. Sodhi, and N. H. Heintz Baculovirus P35 inhibits NO-induced apoptosis in activated macrophages by inhibiting cytochrome c release J. Cell Sci., June 15, 2004; 117(14): 3031 - 3039. [Abstract] [Full Text] [PDF] |
||||
![]() |
S. Hortelano, P. G. Traves, M. Zeini, A. M. Alvarez, and L. Bosca Sustained Nitric Oxide Delivery Delays Nitric Oxide-Dependent Apoptosis in Macrophages: Contribution to the Physiological Function of Activated Macrophages J. Immunol., December 1, 2003; 171(11): 6059 - 6064. [Abstract] [Full Text] [PDF] |
||||
![]() |
S. T. Grey, C. Longo, T. Shukri, V. I. Patel, E. Csizmadia, S. Daniel, M. B. Arvelo, V. Tchipashvili, and C. Ferran Genetic Engineering of a Suboptimal Islet Graft with A20 Preserves {beta} Cell Mass and Function J. Immunol., June 15, 2003; 170(12): 6250 - 6256. [Abstract] [Full Text] [PDF] |
||||
![]() |
A. Castrillo, P. G. Traves, P. Martin-Sanz, S. Parkinson, P. J. Parker, and L. Bosca Potentiation of Protein Kinase C {zeta} Activity by 15-Deoxy-{Delta}12,14-Prostaglandin J2 Induces an Imbalance between Mitogen-Activated Protein Kinases and NF-{kappa}B That Promotes Apoptosis in Macrophages Mol. Cell. Biol., February 15, 2003; 23(4): 1196 - 1208. [Abstract] [Full Text] [PDF] |
||||
![]() |
Y.-C. T. Huang, J. Soukup, S. Harder, and S. Becker Mitochondrial oxidant production by a pollutant dust and NO-mediated apoptosis in human alveolar macrophage Am J Physiol Cell Physiol, January 1, 2003; 284(1): C24 - C32. [Abstract] [Full Text] [PDF] |
||||
![]() |
C.-J. Tsi, Y. Chao, C.-W. Chen, and W. W. Lin Aurintricarboxylic Acid Protects against Cell Death Caused by Lipopolysaccharide in Macrophages by Decreasing Inducible Nitric-Oxide Synthase Induction via Ikappa B Kinase, Extracellular Signal-Regulated Kinase, and p38 Mitogen-Activated Protein Kinase Inhibition Mol. Pharmacol., July 1, 2002; 62(1): 90 - 101. [Abstract] [Full Text] [PDF] |
||||
![]() |
B. Beltran, M. Quintero, E. Garcia-Zaragoza, E. O'Connor, J. V. Esplugues, and S. Moncada Inhibition of mitochondrial respiration by endogenous nitric oxide: A critical step in Fas signaling PNAS, June 25, 2002; 99(13): 8892 - 8897. [Abstract] [Full Text] [PDF] |
||||
![]() |
A. Almeida, J. Almeida, J. P. Bolanos, and S. Moncada Different responses of astrocytes and neurons to nitric oxide: The role of glycolytically generated ATP in astrocyte protection PNAS, December 6, 2001; (2001) 261560998. [Abstract] [Full Text] [PDF] |
||||
![]() |
A. Castrillo, D. J. Pennington, F. Otto, P. J. Parker, M. J. Owen, and L. Bosca Protein Kinase C{epsilon} Is Required for Macrophage Activation and Defense Against Bacterial Infection J. Exp. Med., October 29, 2001; 194(9): 1231 - 1242. [Abstract] [Full Text] [PDF] |
||||
![]() |
P. G. Matz, M. Fujimura, A. Lewen, Y. Morita-Fujimura, and P. H. Chan Increased Cytochrome c-Mediated DNA Fragmentation and Cell Death in Manganese-Superoxide Dismutase-Deficient Mice After Exposure to Subarachnoid Hemolysate Stroke, February 1, 2001; 32(2): 506 - 515. [Abstract] [Full Text] [PDF] |
||||
![]() |
S. HORTELANO, M. CASTILLA, A. M. TORRES, A. TEJEDOR, and L. BOSCÁ Potentiation by Nitric Oxide of Cyclosporin A and FK506-Induced Apoptosis in Renal Proximal Tubule Cells J. Am. Soc. Nephrol., December 1, 2000; 11(12): 2315 - 2323. [Abstract] [Full Text] |
||||
![]() |
S. Hortelano, A. Castrillo, A. M. Alvarez, and L. Bosca Contribution of Cyclopentenone Prostaglandins to the Resolution of Inflammation Through the Potentiation of Apoptosis in Activated Macrophages J. Immunol., December 1, 2000; 165(11): 6525 - 6531. [Abstract] [Full Text] [PDF] |
||||
![]() |
A. Castrillo, M. Mojena, S. Hortelano, and L. Bosca Peroxisome Proliferator-activated Receptor-gamma -independent Inhibition of Macrophage Activation by the Non-thiazolidinedione Agonist L-796,449. COMPARISON WITH THE EFFECTS OF 15-DEOXY-Delta 12,14-PROSTAGLANDIN J2 J. Biol. Chem., August 31, 2001; 276(36): 34082 - 34088. [Abstract] [Full Text] [PDF] |
||||
![]() |
A. M. Cassina, R. Hodara, J. M. Souza, L. Thomson, L. Castro, H. Ischiropoulos, B. A. Freeman, and R. Radi Cytochrome c Nitration by Peroxynitrite J. Biol. Chem., July 7, 2000; 275(28): 21409 - 21415. [Abstract] [Full Text] [PDF] |
||||
![]() |
A. Almeida, J. Almeida, J. P. Bolanos, and S. Moncada Different responses of astrocytes and neurons to nitric oxide: The role of glycolytically generated ATP in astrocyte protection PNAS, December 18, 2001; 98(26): 15294 - 15299. [Abstract] [Full Text] [PDF] |
||||
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |